The proposed research project should extend our knowledge of 1) genetic and physiological controls operative in tetrahydrofolate metabolism 2) the interactions of this metabolic system with other regulatory circuits in the cell. 3) The relation between gene clusters and enzyme aggregates in fungi and the relation of such gene clusters to operons. Mutants altered in tetrahydrofolate metabolism will be analyzed genetically and biochmically. The enzymes will be characterized to see whether they form an aggregate. Eventually the genetic properties of the system will be related to the properties of the enzymes or the enzyme aggregate.